Speeding up Drug Discovery in 3-Dimensions

News

Posted on Friday 15 August 2025

A new synthetic approach to fragment based drug discovery has been developed which will speed up the discovery of new 3-D shaped drugs

Structure of a newly discovered Janus kinase 3 inhibitor and a computational model showing how it binds to the protein

Fragment-based drug discovery is one of the methods used in the development of new drugs. This approach relies on synthetic chemistry but industrialists have highlighted that synthesis is the slowest part of the process, especially when working on 3-D shaped drugs.

To address this, Peter O’Brien and his team at York, in collaboration with AstraZeneca through a Royal Society Industry Fellowship, have developed a modular, programmable synthetic platform for speeding up fragment-based drug discovery.

The team designed a library of 3-D shaped building blocks which systematically explore 3-D chemical space. The building blocks were synthesised on the gram-scale and made commercially available through a partnership with Key Organics. These building blocks can then be easily modified, using pre-established synthetic methods, to yield larger libraries of potential drugs.

This approach was then used in a real-world drug discovery project. On a very short timescale, this led to the discovery of a Janus kinase 3 inhibitor, of relevance in the treatment of autoimmune, autoinflammatory, and allergic diseases.

Notes to editors:

The work has been published in the J. Am. Chem. Soc.